VEGANALYZE

Vitamin B12 Supplementation

Vitamin B12 serves numerous functions in the body. It plays a role in various bodily processes such as the formation of red blood cells, DNA, and myelin sheath. Myelin provides protective coverage for nerve fibers.

Since the plant-based vitamin B12 produced by bacteria only attaches to a few plant-based foods, a deficiency can occur with a vegan diet when B12 reserves are depleted. A vitamin B12 deficiency with corresponding symptoms can also arise after several years if the body hasn't been supplied with B12. The symptoms should not be ignored. Therefore, the body should regularly receive vitamin B12 as a preventive measure.

Vitamin B12 can be absorbed in its unbound form, as found in dietary supplements, through passive diffusion.

Dietary Supplement Product Range

In the market, three unbound forms of cobalamin are primarily available as dietary supplements: methylcobalamin (often referred to as Methyl B12), cyanocobalamin, and hydroxocobalamin (sometimes called hydroxycobalamin). Cyanocobalamin is typically added to foods fortified with B12.

The other forms are found in a wide range of vitamin B12 dietary supplements. This includes sublingual lozenges and powders, oral preparations (drops, tablets, capsules), as well as injections, B12 toothpaste, nasal spray, and B12 patches.

Cyanocobalamin

Most vitamin B12-fortified foods such as soy yogurt or plant-based drinks contain cyanocobalamin as it is the most stable form of cobalamin. Cyanocobalamin is manufactured by pharmaceutical companies at a very low cost. It is not a biologically active form that the body can immediately utilize.

The ingested cyanocobalamin is transported to cells with the help of a transport protein (transcobalamin II) and is taken up through endocytosis 1. The transport protein is then cleaved, and the cyanide molecule is released from the cytoplasm through biochemical processes (cyanocobalamin reductase). The enzyme rhodanase converts cyanide to thiocyanate. Subsequently, it is excreted from the body through the kidneys.

Depending on the needs, the "free" cobalamin is now supplemented with a methyl group or a 5'-deoxyadenosine molecule. Methylcobalamin and 5′-deoxyadenosylcobalamin (often simply called adenosylcobalamin) are the two active forms of cobalamin.

Cyanide is a poison. Cyanide is naturally present in foods such as flaxseeds, legumes, and apples (seeds) 2. Consuming high amounts of cyanocobalamin can be harmful to the kidneys. However, the amount of cyanide is minuscule, with 20 µg per 1,000 µg of cyanocobalamin 3. Distributed across individual cyanocobalamin dosages, the following cyanide components result:

The molar mass of vitamin B12 is 1.355 g/mol, and that of cyanide is 27 g/mol. Here is an example calculation for the 25 µg dosage: ((25 µg) x (27 (g/mol))) / (1355 (g/mol)) = 0.498 µg of cyanide.

As a guideline for the maximum daily intake of cyanide, the ADI (Acceptable Daily Intake) exists. It was set at 0.05 mg/kg body weight in 1971 4. So, a healthy person weighing 70 kg can consume up to 3.5 mg of cyanide per day without causing any health damage. Therefore, toxic effects of cyanocobalamin on the body are highly unlikely. For comparison, 10 g of flaxseed contains approximately 1.4 mg of cyanide (Calculation: 140 ppm (μg/g) x 10 g flaxseed = 1,400 µg) 5.

Patients with cyanide poisoning, kidney dysfunction, or renal failure can accumulate cyanide in their bodies 67. Therefore, according to scientists, high dosages of oral cyanocobalamin should be avoided in these patients, and instead, methylcobalamin or hydroxycobalamin should be used.

The same applies to individuals with cobalamin C defect, who have impaired conversion of vitamin B12 into the two metabolically active forms, methylcobalamin and adenosylcobalamin 8. Smokers should also avoid cyanocobalamin 9.

Vitamin C can reduce the absorption amount of vitamin B12 10. High doses of vitamin C or foods rich in vitamin C should be avoided within one hour before or after taking cyanocobalamin.

Supplements containing cyanocobalamin may contain benzyl alcohol (preservative). Therefore, it should not be administered to infants and young children, as severe and sometimes fatal nervous system disorders and other side effects may occur 11. That's why supplementation during pregnancy should also not be done with cyanocobalamin and only in consultation with a doctor.

Side effects of cyanocobalamin are rare. However, symptoms such as allergic reactions like rash, itching/swelling (especially of the face, tongue, and throat), severe dizziness, and difficulty breathing should be monitored for 12.

We recommend avoiding cyanocobalamin to prevent further increase in cyanide levels, allowing more flexibility in consuming cyanide-rich foods (such as flaxseeds) or foods enriched with vitamin B12 (table).

Methylcobalamin

Methylcobalamin is an active form of cobalamin and occurs naturally (produced by bacteria). Nevertheless, like cyanocobalamin, methylcobalamin is transported to the cell plasma, where the methyl group is initially cleaved. Afterwards, depending on the need, cyanocobalamin is further converted or stored.

Methylcobalamin has lower stability compared to cyanocobalamin due to its higher sensitivity to light, heat, and oxygen. Therefore, it should be stored in a dark place. Due to its greater instability, it is currently believed that larger amounts of methylcobalamin need to be consumed than cyanocobalamin to achieve the same effect. Scientists have concluded that supplementation with methylcobalamin or adenosylcobalamin is unlikely to be superior to cyanocobalamin in the prevention or treatment of cobalamin deficiency 13.

If you want to supplement your diet with vitamin B12, you should opt for methylcobalamin. The European Food Safety Authority (EFSA) has no safety concerns regarding the supplementation of methylcobalamin 14.

Adenosylcobalamin

This form of vitamin B12 is active in the body, just like Methylcobalamin. Adenosylcobalamin is also available in pharmacies under the name Dibencozide. Relevant scientific studies on the effectiveness of supplementing with Adenosylcobalamin are not yet available. The European Food Safety Authority does not have any safety concerns regarding Adenosylcobalamin either 15.

Hydroxycobalamin

Hydroxycobalamin is usually injected in cases of acute vitamin B12 deficiency. Additionally, it is used, like cyanocobalamin, as an additive to enrich foods with B12. Whether it is vegan hydroxycobalamin or not should be inquired with the provider. Injections are highly effective because they bypass the digestive tract and a large portion goes directly into the bloodstream. But who wants to inject themselves with vitamin B12 regularly? Furthermore, allergic reactions are often observed with this form of supplementation 16. This type of treatment should be done in consultation with a doctor, as there can also be side effects.

Direct Absorption of Vitamin B12

Many B12 supplements contain other vitamins (including folic acid, which is needed for methionine synthase) and minerals. With a balanced diet, all other nutrients are usually consumed in sufficient amounts, so vitamin B12 should be supplemented "purely".

Since unbound vitamin B12 can also be absorbed through the oral mucosa under the tongue, it is advisable to let the corresponding preparations dissolve in the mouth to improve absorption (see also the next section).

Absorption of B12 Supplements

Those who want to meet their vitamin B12 requirement once a week through a dietary supplement need much higher amounts of B12 compared to those who rely on supplementation multiple times a week. This is due to different absorption rates.

The table below shows the absorption rates through oral dietary supplementation. 17 18:

The human body can absorb more vitamin B12 from a smaller dosage than from a larger one. A smaller dose (e.g., 50 μg) absorbs a significantly higher percentage of vitamin B12 compared to a larger dose (1,000 μg). Therefore, if B12 is consumed less frequently, the total amount must be higher to absorb the desired quantity. It is better to take multiple smaller dosages several times a week than a single larger dosage.

The sublingual absorption (taken under the tongue through oral mucosa) is shown to be equally effective as the oral (through the digestive tract) route at a dosage of 500 µg of vitamin B12 19 20.

How much to supplement?

The previous section serves as the basis for frequency and dosage. To meet the daily requirement (or weekly requirement) of vitamin B12, it is possible to supplement either twice a day, once a day, or twice a week. Since vitamin B12 can be stored in the body, supplementation does not need to be done every day.

For Methylcobalamin and Adenoslycobalamin, there is a lack of studies. The following values are recommendations for supplementing with Cyanocobalamin but can also serve as a guideline for supplementing with Methylcobalamin and Adenoslycobalamin 21:

This shows that the requirement for a 14- to 64-year-old can be met with a dosage of 2 to 3.5 μg twice daily, or with 25 to 100 μg per day, or with 1,000 μg twice weekly.

The Vegan Society recommends the following values to meet the requirement 22:

• consume vitamin B12-fortified foods with each meal (for a total of 3 μg per day)
• or take a daily B12 supplement with at least 10 μg
• or take a supplement with at least 2,000 μg per week

High doses of over 5,000 μg per week should be avoided due to a lack of studies.

To ensure that infants are also provided with vitamin B12 through breast milk, mothers should consider a correspondingly higher intake of B12 in their diet (see vitamin B12 daily requirement).